鉴定出一个含有CGG重复序列的基因（FMR-1），该基因与脆性X综合征中表现出长度变异的断点簇区域一致。

Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome.

作者信息

Verkerk A J, Pieretti M, Sutcliffe J S, Fu Y H, Kuhl D P, Pizzuti A, Reiner O, Richards S, Victoria M F, Zhang F P

机构信息

Department of Clinical Genetics, Erasmus University Rotterdam, The Netherlands.

出版信息

Cell. 1991 May 31;65(5):905-14. doi: 10.1016/0092-8674(91)90397-h.

DOI:10.1016/0092-8674(91)90397-h

PMID:1710175

Abstract

Fragile X syndrome is the most frequent form of inherited mental retardation and is associated with a fragile site at Xq27.3. We identified human YAC clones that span fragile X site-induced translocation breakpoints coincident with the fragile X site. A gene (FMR-1) was identified within a four cosmid contig of YAC DNA that expresses a 4.8 kb message in human brain. Within a 7.4 kb EcoRI genomic fragment, containing FMR-1 exonic sequences distal to a CpG island previously shown to be hypermethylated in fragile X patients, is a fragile X site-induced breakpoint cluster region that exhibits length variation in fragile X chromosomes. This fragment contains a lengthy CGG repeat that is 250 bp distal of the CpG island and maps within a FMR-1 exon. Localization of the brain-expressed FMR-1 gene to this EcoRI fragment suggests the involvement of this gene in the phenotypic expression of the fragile X syndrome.

摘要

脆性X综合征是遗传性智力迟钝最常见的形式，与Xq27.3处的一个脆性位点相关。我们鉴定出了跨越脆性X位点诱导的易位断点（与脆性X位点一致）的人类酵母人工染色体（YAC）克隆。在一个由四个黏粒重叠群组成的YAC DNA中鉴定出一个基因（FMR - 1），该基因在人类大脑中表达一种4.8 kb的信息。在一个7.4 kb的EcoRI基因组片段内，包含位于一个CpG岛远端的FMR - 1外显子序列（先前已证明在脆性X患者中该CpG岛发生高甲基化），是一个脆性X位点诱导的断点簇区域，在脆性X染色体中表现出长度变异。该片段包含一个长的CGG重复序列，位于CpG岛下游250 bp处，定位于FMR - 1外显子内。在大脑中表达的FMR - 1基因定位于这个EcoRI片段，提示该基因参与了脆性X综合征的表型表达。